Cyanide, addition with

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

VI. Palladium Cyanide Addition with Hydride Elimination... 

Butadiene. 100 ml. of 0.30M CoClj and 100 ml. of 1.54M KCN in an atmosphere of butadiene were employed. Injection of isopropyl iodide was followed by cyanide addition with vigorous stirring. The solution turned red. On completion of gas evolution, a gas sample was taken for analysis. It showed the presence of 19.2% propane, 33.9% propylene, 1.00% 1-butene, 1.81% fmrw-2-butene, 0.14% ci 5-2-butene the remainder was butadiene. The mass spectrum showed no C7 product. 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Racemic pantolactone is prepared easily by reacting isobutyraldehyde (15) with formaldehyde ia the presence of a base to yield the iatermediate hydroxyaldehyde (16). Hydrogen cyanide addition affords the hydroxy cyanohydria (17). Acid-cataly2ed hydrolysis and cyclization of the cyanohydria (17) gives (R,3)-pantolactone (18) ia 90% yield (18). 

Finally, examine transition states for cyanide addition cyanide+formaldehyde, cyanide+acetone, cyanide+ benzophenone) What relationship, if any, is there between the length of the forming CC bond and the various carbonyl properties determined above Try to rationalize what you find, and see if there are other structural variations that can be correlated with carbonyl reactivity. 

Inclusion of additional alkyl groups on the aromatic ring leads to decongestants with longer duration of action. Thus, reaction of the arylacetonitrile, 109, obtainable from hydrocarbon, 107, by chloromethylation (108), followed by displacement of the halogen by means of cyanide ion with ethylenediamine, leads to xylometazoline (111). The analogous reaction of the oxygenated derivative, 110, affords oxymetazoline (112). ... 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Tin and HCl reduce out the ben/.ylic OH from (43) in high yield.The Mannich base (45) decomposes to (41) simply on heating. Cyanide addition gives (46) which can be hydrolysed to (40), but a short cut is to hydrolyse to amide (47) and reduce out the carbonyl group by the Clemmensen method (Table T 24.1). Under these conditions the amide is hydrolysed to the acid. Cyclisation to (38) occurs with strong acid, acid anhydrides, or by AlClg-catalysed reaction of the acid chloride. 

Arenes, on complexation with Cr, Fe, Mn, and so forth, acquire strongly electrophilic character such complexes in reactions with nucleophiles behave as electrophilic nitroarenes.71 Synthesis of aromatic nitriles via the temporary complexation of nitroarenes to the cationic cyclopentadienyliron moiety, cyanide addition, and oxidative demetalation with DDQ has been reported (Eq. 9.43).72... 

Cyanide Addition of ascorbic acid, then render alkaline to pH 11-12 with sodium hydroxide This determinand must be preserved immediately. Need for separate container. Any residual chlorine must be removed with ascorbic acid. 

Maruoka and co-workers recently reported an example of a Zr-catalyzed cyanide addition to an aldehyde [64]. As is also illustrated in Scheme 6.20, the reaction does not proceed at all if 4 A molecular sieves are omitted from the reaction mixture. It has been proposed that the catalytic addition proceeds through a Meerwein—Ponndorf—Verley-type process (cf. the transition structure drawn) and that the crucial role of molecular sieves is related to facilitating the exchange of the product cyanohydrin oxygen with that of a reagent acetone cyanohydrin. The example shown is the only catalytic example reported to date the other reported transformations require stoichiometric amounts of the chiral ligand and Zr alkoxide. 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

To enhance the efficiency of the cyanide addition, these workers subsequently reported a three-component asymmetric synthesis of amino nitriles that avoids the use of the previously mentioned undesirable stannane [74], Thus, as illustrated in Scheme 6.23, treatment of the requisite aniline and aldehyde with HCN (toxic but cheap and suitable for industrial use) at —45°C in the presence of 2.5 mol% 65 leads to the formation of 67 with 86 % ee and in 80 % yield. As was mentioned above in the context of catalytic asymmetric three-component alkylations of imines (see Scheme 6.18), the in situ procedure is particularly useful for the less stable aliphatic substrates (cf. 71—73, Scheme 6.23). The introduction of the o-Me group on the aniline is reported to lead to higher levels of asymmetric induction, perhaps because with the sterically less demanding aliphatic systems, the imine can exist as a mixture of interconverting cis and trans isomers. 

The coupling of cyanides ions with aryl radicals is an interesting example where quantitative kinetic data are available.30 The forming bond is strong, but this favorable factor is counteracted, in terms of driving force, by the fact that °./x- [second term in equation (3.24)] is very positive (in other words, CN is a hard nucleophile). In addition, the large value of Drx r +x is unfavorable in terms of the intrinsic barrier. Overall, the presence of electron-withdrawing substituents is necessary to allow the... 

The fate of the PhSO- liberated through either (27b) or (29) varies depending upon reaction conditions. In some cases, as in the reaction of cyanide ion with PhS(0)SPh in a CN-/HCN buffer (Kice and Liu, 1979), it is converted to PhSNu, presumably through protonation to PhSOH and subsequent reaction of the sulfenic acid with additional nucleophile (30). On the... 

A simple tandem Michael addition of cyanide ion with alkylation on Jt-deficient alkenes has been effected on diethyl l -methylpropylidenecyanoacetates and benzyl-idenemalonates using benzyltriethylammonium chloride to yield 2-alkyl-2,3-dicyanopropanoates and the analogous 2-ethoxycarbony derivatives [44]. 

Kiliani-Fischer synthesis is a means of lengthening the carbon backbone of a carbohydrate. The process begins with the reaction of hydrogen cyanide (HCN) with an aldehyde to produce a cyanohydrin. Treatment of the cyanohydrin with barium hydroxide followed by acidification yields an aldose with an additional carbon atom, as shown in Figure 16-16. The formation of the cyanohydrin creates a new chiral center as a racemic mixture. 

In the presence of catalytic amounts of both sodium -toluenesulfinate and potassium cyanide, the reaction of benzaldehyde with 4-chloroquinazoline 89 gave 4-benzoylquinazoline 90 in good yield <1998H(47)407>. The reaction involves activation of the benzaldehyde by cyanide addition, and activation of the quinazoline as the 4-toluenesulfonyl derivative. 

Nitro compounds can be cyclized to give quinolines in two non-reductive processes. In the first, an o-nitro-cinnamate or -cinnamonitrile is cyclized by treatment with cyanide ions, via the cyanide addition product as generalized in equation (29). The reaction has been... 

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